IMPC study shows that genes essential to life are enriched in human and mouse

Wednesday, 14 September 2016

Roughly a third of all genes in the mammalian genome are essential for life. A new article in Nature, from an international, multi-institutional research team including many INFRAFRONTIER partners, describes the large-scale discovery of those genes and how it will impact understanding of mammalian development and human disease. The International Mouse Phenotyping Consortium, which is generating and phenotyping (assessing the physiological characteristics of knockout mutations for all of the protein-coding genes in the mouse genome. The Consortium aims to discover new functions for the roughly 20,000 genes shared with humans, providing a platform for dissecting the mechanisms of human disease.

Results published in Nature

The Nature study, published 14 September, reports the results of the first 1,751 genes characterized by the IMPC, including the finding that nearly one third are essential for life. This includes 410 lines that are fully lethal, and an additional 198 for which fewer than half of the expected number of mutants were identified. Using a new, standardized phenotyping platform and mouse lines on a single C57BL/6N genetic background, the researchers established both the time of embryonic death and the nature of the lethal phenotypes for these lines, discovering many novel phenotypes that shed light on the function of these genes. The incorporation of high-resolution 3D imaging and automated, computational analysis of the images allowed the team to gather detailed phenotypic data rapidly, thus enabling the discovery of new phenotypes at an unprecedented scale. The group also showed that identification of essential genes in the mouse provides a window on human disease, including the discovery of a number of novel cases where human disease genes overlap with essential genes. All data and images generated by the project are available to the research community, disseminated via an open-source web portal (www.mousephenotype.org) in real time without embargo. The mouse models generated are also available to other researchers who may be investigating particular pathways or disease phenotypes.